Abstract The histological features of familial cerebral amyloid angiopathy (British type) with non-neuritic amy- loid plaque formation (FAB) include deposition of amy- loid, (supposedly associated with the C-terminal frag- ments of both α- and β-tubulin), in small cerebral and spinal arteries, hippocampal amyloid plaques and neu- rofibrillary tangles (NFTs) as well as ischaemic white matter changes. In the present study we report on the cy- toskeletal pathology that occurs in association with FAB. Sections from the hippocampus and cerebellum of three cases from three unrelated families were stained with sil- ver impregnation methods and antibodies to antigens in- cluding tau, neurofilaments, ubiquitin and glial fibrillary acidic protein. Electron microscopic examination of the hippocampus was carried out in one case. All hippocam- pal subregions contained large numbers of NFTs and neu- ropil threads (NT), which were stained with both phos- phorylation-dependent and phosphorylation-independent tau antibodies and ultrastructurally were found to be com- posed of paired helical filaments (PHFs). Although the majority of the amyloid plaques were of the non-neuritic type, distended PHF-containing and tau-positive neurites were seen in close proximity of a minority of the hip- pocampal plaques. The perivascular amyloid deposits of the cerebellum contained numerous ubiquitin-positive granular elements similar to those seen in cerebellar Aβ amyloid plaques in Alzheimer’s disease. In FAB se- vere cytoskeletal pathology is present in areas most af- fected by amyloid plaque deposits, thus suggesting a lo- calised neurotoxic effect of the poorly characterised amy- loidogenic peptide characteristic of this condition. Key words Amyloid angiopathy · Amyloid plaque · British type · Neurofibrillary tangle · Paired helical filament Introduction Familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation (FAB) is an auto- somal dominant condition, which clinically is charac- terised by progressive spastic tetraparesis, cerebellar ataxia and dementia [21, 28–30]. Pathological findings, which to date have been documented in a small number of cases, include extensive cerebral amyloid angiopathy, hip- pocampal amyloid plaques and neurofibrillary tangles (NFTs), cerebellar degeneration due to severe amyloid angiopathy with perivascular plaques and white matter degeneration similar to that seen in Binswanger’s disease [15, 21, 29, 30]. Light and electron microscopic examina- tion of one such case showed that the majority of the hippocampal amyloid plaques are primarily of the “non- neuritic” type [21]. Although subsequent immunohisto- chemical examination of the same case with a number of antibodies to known amyloidogenic peptides including Aβ-peptide, prion protein (PrP), transthyretin and cystatin C failed to identify the nature of the amyloid [14], a more recent biochemical study has suggested that this may be related to the C-terminal fragments of both α- and β-tubu- lin [2]. Although FAB was previously considered to be re- stricted to a single, large British pedigree with 26 affected members documented [21], at least two further unrelated British families with similar clinical presentation and pathological findings have been described [12, 18]. The aims of this study were to define the immunohis- tochemical profile of the cytoskeletal pathology that oc- T. Revesz · J. L. Holton · B. Doshi · B. H. Anderton · F. Scaravilli · G. T. Plant Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation Acta Neuropathol (1999) 97 :170–176 © Springer-Verlag 1999 Received: 2 June 1998 / Revised, accepted: 11 August 1998 REGULAR PAPER T. Revesz () · J. L. Holton · F. Scaravilli Department of Neuropathology, Institute of Neurology, Queen Square, London WC1N 3 BG, UK e-mail: T.Revesz@ion.ucl.ac.uk, Fax: +44-171-916 9546 B. Doshi Department of Neuropathology, Institute of Psychiatry, London, UK B. H. Anderton Department of Neuroscience, Institute of Psychiatry, London, UK G. T. Plant National Hospital for Neurology and Neurosurgery, London, UK